AJP - Regulatory, Integrative and Comparative Physiology, Vol 249, Issue 5 563-R569, Copyright © 1985 by American Physiological Society
Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration
R. P. Cornell
The influence of restricting gut-derived endotoxin availability on liver
regeneration after partial hepatectomy was evaluated. Partial hepatectomy
was performed by 67% liver resection of ether-anesthetized rats. Liver
regeneration was quantified after partial hepatectomy by [3H]thymidine
incorporation into hepatic DNA; endotoxemia due to absorption of endogenous
endotoxin from the gut into the portal circulation was determined by
qualitative lysate assay of perchloric acid-extracted plasma samples, and
plasma levels of the hepatotrophic factors insulin and glucagon were
measured by radioimmunoassay. Treatments to restrict gut-derived endotoxin
included chronic gavage with neomycin and cefazolin for gut sterilization,
chronic gavage with cholestyramine to bind endotoxin within the gut,
subcutaneous administration of polymyxin B to neutralize the lipid A
portion of circulating endotoxin, intraperitoneal induction of endotoxin
tolerance by progressively higher doses of endotoxin, and experimentation
with isolator-reared defined flora Fisher rats that were Gram-negative
bacteria deficient and therefore endotoxin deficient. All treatments to
restrict endogenous endotoxin impaired DNA synthesis in regenerating livers
particularly 21 h posthepatectomy when replication was increasing most
rapidly in normal rats. We hypothesize that impairment of DNA synthesis
after partial hepatectomy in endotoxin-restricted animals was due to the
observed lack of normal systemic endotoxemic as well as hyperinsulinemic
and hyperglucagonemic responses to 67% liver resection.
